EP0531524A1 - Supositoire a liberation entretenue - Google Patents

Supositoire a liberation entretenue Download PDF

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Publication number
EP0531524A1
EP0531524A1 EP90907483A EP90907483A EP0531524A1 EP 0531524 A1 EP0531524 A1 EP 0531524A1 EP 90907483 A EP90907483 A EP 90907483A EP 90907483 A EP90907483 A EP 90907483A EP 0531524 A1 EP0531524 A1 EP 0531524A1
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EP
European Patent Office
Prior art keywords
release
sustained
acid
diclofenac sodium
acidic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP90907483A
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German (de)
English (en)
Other versions
EP0531524B1 (fr
EP0531524A4 (en
Inventor
Masami 1-23-809 Azuma Murata
Harumi 1-33-1 Kaga Kishi
Takashi 4-12-4 Ohsakidai Narui
Shuichi 2-2-11-102 Azuma Kasai
Akira 886-16 Shikawatashi Iwasa
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SSP Co Ltd
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SSP Co Ltd
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Publication date
Application filed by SSP Co Ltd filed Critical SSP Co Ltd
Publication of EP0531524A1 publication Critical patent/EP0531524A1/fr
Publication of EP0531524A4 publication Critical patent/EP0531524A4/en
Application granted granted Critical
Publication of EP0531524B1 publication Critical patent/EP0531524B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S424/00—Drug, bio-affecting and body treating compositions
    • Y10S424/15—Suppositories

Definitions

  • the present invention relates to a sustained-release suppository preparation.
  • Suppository has a number of advantages. It not only can avoid decomposition of drugs by acid or enzyme in gastrointestinal tract when the drugs are orally administered or can avoid irritation stimulation to gastrointestinal mucosa which is caused by direct contact of drugs with mucosa, but also is physiologically less affected by such factors as variations of pH in gastrointestinal tract, the gastric empty rate, mobility of gastrointestinal tract, mutual actions between food components, and the like. In addition, suppository is safer and easier to administer than injection. Thus, it is a form of preparation which is applicable even to infant or elderly patients.
  • the present invention provides a sustained-release suppository preparation characterized by comprising an acidic drug or a salt thereof which can be absorbed by rectal administration and an acidic compound or a pH buffering agent.
  • Figure 1 is a drawing showing the result of the release test according to Test Example 1, wherein the relationship between the released percent of diclofenac sodium and time elapsed is shown.
  • Figure 2 is a drawing showing the result of the release test according to Test Example 2, wherein the relationship between the released percent of diclofenac sodium and the time elapsed is shown.
  • Figure 3 is a drawing showing the result of the release test according to Test Example 3, wherein the relationship between the released percent of the active component and the time elapsed is shown.
  • Figure 4 is a drawing showing the relationship between the concentration of diclofenac sodium in plasma and the time after the administration to rabbits according to Test Example 4.
  • Figure 5 is a drawing showing the result of the release test according to Test Example 5, wherein the relationship between the released percent of diclofenac sodium and the time elapsed is shown.
  • Figure 6 is a drawing showing the relationship between the concentration of diclofenac sodium in plasma and the time elapsed after the administration to rabbits according to Test Example 5.
  • acidic drugs or salts thereof used in the present invention there are no specific limitations as to acidic drugs or salts thereof used in the present invention so long as they can sufficiently be absorbed by rectal administration.
  • acidic drugs or salts thereof include flurazepam, nimetazepam, nitrazepam, perlapine, estazolam, haloxazolam, sodium valproate, sodium cromoglycate, primidone, alclofenac, perisoxal citrate, clidanac, indomethacin, sulpyrine, flufenamic acid, ketoprofen, sulindac, metiazinic acid, tolmetin sodium, fentiazac, naproxen, fenbufen, protizinic acid, pranoprofen, flurbiprofen, diclofenac sodium, mefenamic acid, ibuprofen, aspirin, dextran sulfate, carindacillin sodium, and
  • acidic compounds or pH buffering agents so long as they are capable of acidifying the site where the suppository is administered.
  • acidic compounds are fumaric acid, tartaric acid, adipic acid, citric acid, malic acid, succinic acid, ascorbic acid, maleic acid, malonic acid, phosphoric acid, butyric acid, lactic acid, acetic acid, and the like. They can be used either singly or in their two or more combinations.
  • buffering agents combinations with said acids and salts thereof can be used.
  • an amount which can give the target sustained-release suppository is sufficient and such an amount varies depending on the characteristic of the drug used.
  • an amount of 0.02 part by weight or more per 1 part by weight of the acidic drug or a salt thereof is generally applicable.
  • any base components commonly used for suppositories can be used as a base component of the suppository preparation of the present invention, including those derived from animal, vegetable or mineral origins, and materials partially or totally synthesized.
  • Specific examples given of such base components include oils and fats of animals or vegetable origin, e.g., olive oil, corn oil, castor oil, cottonseed oil, wheat germ oil, cacao butter, hydrogenated oils, etc.; hydrocarbons, e.g., squalane, petrolatum, solid paraffin, liquid paraffin, etc.; and waxes, e.g., jojoba oil, carnauba wax, bees wax, lanolin, etc.
  • fatty acid esters glycerol mono-, di-, or triglycerides of medium or higher fatty acid, such as saturated linear fatty acid, e.g., lauric acid, myristic acid, palmitic acid, stearic acid, etc., or unsaturated linear fatty acid, e.g., oleic acid, linoleic acid, linolenic acid, etc, are given.
  • saturated linear fatty acid e.g., lauric acid, myristic acid, palmitic acid, stearic acid, etc.
  • unsaturated linear fatty acid e.g., oleic acid, linoleic acid, linolenic acid, etc.
  • sustained-release suppository preparations of the present invention after the addition of an acidic drug or a salt thereof and an acidic compound or buffering agent to the base component, can be made in the form of solid suppositories, softgelation encapsule suppositories by soft gelatin or of rectal injection type ointments.
  • additives such as absorption enhancers, preservatives, stabilizers, surfactants, perfumes, pigments, purified water, and the like may be added to the suppository preparation of the present invention.
  • polymers, various types of carriers, gelling agents, and the like may be added in order to adjust the release rate of the drug.
  • polymers there are no specific limitations as to the types of polymers so long as such polymers can be used for the purpose of adjusting the release rate of drugs.
  • Specific examples include water insoluble polymers, e.g., ethylcellulose, aminoalkyl methacrylate copolymer, polyvinyl acetate, etc.; intestinally soluble polymers, e.g., cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, carboxymethylethylcellulose, stylene-acrylic acid copolymer, methacrylic acid copolymer, maleic acid anhydride copolymers, etc.; acid soluble polymers, e.g., polyvinylacetaldiethylamino acetate, aminoalkyl-methacrylate copolymer E, etc.; water-soluble polymers, e.g., hydroxypropylmethylcellulose, methylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, arginic acid, sodium
  • Polymers are used when a pharmaceutical composition comprising an acidic drug or a salt thereof is encapsulated into microcapsules or granulated.
  • a carrier can help make the granulation process easier or adjust the rate of release of the drug.
  • Examples of carriers include, but not limited to, organic compound powders such as fructose, glucose, lactose, sucrose, mannitol, starch, dextrin, ⁇ -starch, hydroxypropyl starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose, and the like, and inorganic compound powders such as light silicic anhydride, diatomaceous earth, magnesium silicate, aluminum silicate, calcium sulfate, calcium phosphate, precipitated calcium carbonate, talc, and the like.
  • organic compound powders such as fructose, glucose, lactose, sucrose, mannitol, starch, dextrin, ⁇ -starch, hydroxypropyl starch, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose, and the like
  • inorganic compound powders such as light silicic anhydride, diatomaceous earth, magnesium silicate,
  • microcapsules prepared from the drug composition comprising an acidic drug or a salt thereof by a conventional method are dispersed into a base component to which an acidic compound or a pH buffering agent is incorporated, or microcapsules prepared from the drug composition comprising an acidic drug or a salt thereof and an acidic compound or a pH buffering agent are dispersed into a suppository base component.
  • an acidic drug or a salt thereof and a polymeric compound are kneaded and granulated and the granules are dispersed into a base component to which an acidic compound or a pH buffering agent is incorporated, or an acidic drug or a salt thereof, an acidic compound or a pH buffering agent, and a polymeric compound are kneaded and granulated and the granules are dispersed into a suppository base component.
  • the polymeric compound may be used for kneading after dissolved in a suitable solvent or the polymers in a powdery form may be kneaded with a suitable solvent after mixing with other components.
  • Organic or inorganic gelling agents which can form a matrix in the base component or after the base component has melted or dissolved may be used as the gelling agent.
  • examples are pectin, chitin, chitosan, cross-linked polyacrylamide, polyacrylic acid, arginic acid, sodium arginate, gelatin, agar, acacia, xanthane gum, guar-gum, carboxyvinyl polymer, polyvinyl alcohol, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, aminoalkyl-methacrylate copolymer, light silicic anhydride, aluminum hydroxide, magnesium hydroxide, and the like.
  • a method preparing the sustained-release suppository preparation by dispersing or dissolving a portion of said acidic drug in the base component and adding said microcapsules or granules to the solution or the dispersion, a method of preparing the sustained-release suppository preparation as a multi-layered suppository having two or more layers with different release rates, or a method of preparing the sustained-release suppository preparation as a suppository having a core and two or more layers with different release rates.
  • the present invention is illustrated by way of examples of suppositories in which non-steroidal anti-inflammatory drugs are used, among suppositories for local or systemic administration. These examples are not intended to be limiting of the present invention.
  • Diclofenac sodium and fumaric acid were suspended in molten Witepsol H5 (a product of Dynamit Nobel) and processed according to a conventional method to obtain sustained-release suppository preparations having compositions shown in Table 1.
  • Diclofenac sodium and tartaric acid were suspended in molten Witepsol H5 and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Diclofenac sodium 2.5 g Tartaric acid 16.0 g
  • Witepsol H5 81.5 g
  • Diclofenac sodium and ascorbic acid were suspended in molten Witepsol H5 and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Diclofenac sodium 2.5 g Ascorbic acid 16.0 g
  • Witepsol H5 81.5 g
  • Indomethacin and fumaric acid were suspended in molten Witepsol H5 and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Indomethacin 2.5 g Fumaric acid 16.0 g
  • Witepsol H5 81.5 g
  • Ketoprofen and fumaric acid were suspended in molten Witepsol H5 and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Diclofenac sodium and sodium dihydrogenphosphate were suspended in molten Witepsol H5 and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Diclofenac sodium 2.5 g
  • Sodium dihydrogenphosphate 16.0 g
  • Witepsol H5 81.5 g
  • Mefenamic acid and adipic acid were suspended in molten Polyethylene glycol 1540 (manufactured by Nippon Oil and Fats Co.) and poured into containers to obtain sustained-release suppositories, each weighing 1 g. Mefenamic acid 25.0 g Adipic acid 16.0 g Polyethylene glycol 1540 59.0 g Total 100.0 g
  • Metiazinic acid and citric acid were suspended in molten Isocacao MH-35 (manufactured by Kao Corp.) and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Disodium cromoglycate and tartaric acid were suspended in molten cacao butter and filled into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Tartaric acid 16.0 g
  • Cacao butter 81.5 g
  • Diclofenac sodium and fumaric acid were suspended into macrogole (400) and encapsulated into soft capsules to obtain sustained-release suppositories, each weighing 1 g.
  • Diclofenac sodium 2.5 g Fumaric acid 16.0 g Macrogole 400 41.5 g Total 60.0 g
  • Microcapsules were prepared from a mixture of diclofenac sodium and fumaric acid by a solvent evaporation method. The microcapsules were suspended in Witepsol H5 and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Diclofenac sodium 2.5 g Fumaric acid 1.0 g Aminoalkyl methacrylate copolymer 1.0 g Magnesium stearate 0.5 g Total 5.0 g Microcapsules (Containing 50% of diclofenac sodium) 5.0 g Witepsol H5 95.0 g Total 100.0 g
  • Microcapsules were prepared from a mixture of diclofenac sodium and fumaric acid by a solvent evaporation method. The microcapsules were suspended in molten Pharmaso B-105 (manufactured by Nippon Oil and Fats Co.) and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Diclofenac sodium 2.5 g Fumaric acid 1.0 g Hydroxypropylcellulose 1.0 g Magnesium stearate 0.5 g Total 5.0 g Microcapsules (Containing 50% of diclofenac sodium) 5.0 g Pharmasol B-105 95.0 g Total 100.0 g
  • Diclofenac sodium, sodium arginate, and fumaric acid were suspended in molten Witepsol H5 and poured into containers to obtain sustained-release suppositories, each weighing 1 g.
  • Diclofenac sodium and light silicic anhydride were kneaded with a solution of methacrylic acid copolymer L in ethanol, dried and pulverized to obtain granules. The granules and fumaric acid were suspended in molten Witepsol H15 and poured into containers to obtain sustained-release suppositories, each weighing 1.8 g.
  • Diclofenac sodium 5.0 g Fumaric acid 8.0 g
  • Light silicic anhydride 25.5 g Methacrylic acid copolymer L 5.0 g Witepsol H15 136.5 g Total 180.0 g
  • Diclofenac sodium and light silicic anhydride were kneaded with a solution of polyvinylpyrrolidone in ethanol, dried and pulverized to obtain granules. The granules and fumaric acid were suspended in molten Witepsol H15 and poured into containers to obtain sustained-release suppositories, each weighing 1.8 g.
  • Diclofenac sodium 5.0 g Fumaric acid 8.0 g
  • Light silicic anhydride 25.5 g
  • Polyvinylpyrrolidone 5.0 g Witepsol H15 136.5 g Total 180.0 g
  • Diclofenac sodium and light silicic anhydride were kneaded with a solution of methacrylic acid copolymer S in ethanol, dried and pulverized to obtain granules. The granules and fumaric acid were suspended in molten Witepsol H15 and poured into containers to obtain sustained-release suppositories, each weighing 1.8 g.
  • Diclofenac sodium 5.0 g Fumaric acid 8.0 g
  • Light silicic anhydride 25.5 g Methacrylic acid copolymer S 5.0 g Witepsol H15 136.5 g Total 180.0 g
  • Diclofenac sodium and light silicic anhydride were kneaded with a solution of hydroxypropylmethylcellulose in ethanol, dried and pulverized to obtain granules. The granules and fumaric acid were suspended in molten Witepsol H15 and poured into containers to obtain sustained-release suppositories, each weighing 1.8 g.
  • Diclofenac sodium 5.0 g Fumaric acid 8.0 g
  • Light silicic anhydride 25.5 g Hydroxypropylmethylcellulose 5.0 g Witepsol H15 136.5 g Total 180.0 g
  • Diclofenac sodium and light silicic anhydride were kneaded with a solution of ethylcellulose in ethanol, dried and pulverized to obtain granules. The granules and fumaric acid were suspended in molten Witepsol H15 and poured into containers to obtain sustained-release suppositories, each weighing 1.8 g.
  • Diclofenac sodium 5.0 g Fumaric acid 8.0 g
  • Diclofenac sodium and methacrylic acid copolymer L were kneaded with ethanol, dried and pulverized to obtain granules. The granules and fumaric acid were suspended in molten Witepsol H15 and poured into containers to obtain sustained-release suppositories, each weighing 1.8 g. Diclofenac sodium 5.0 g Fumaric acid 8.0 g Methacrylic acid copolymer L 5.0 g Witepsol H15 162.0 g Total 180.0 g
  • Diclofenac sodium and light silicic anhydride were kneaded with a solution of methacrylic acid copolymer L in ethanol, dried and pulverized to obtain granules. The granules and fumaric acid were suspended in molten Witepsol H15 and poured into containers to obtain sustained-release suppositories, each weighing 1.8 g.
  • Diclofenac sodium 5.0 g Fumaric acid 8.0 g
  • Light silicic anhydride 25.5 g Methacrylic acid copolymer L 5.0 g Witepsol H15 136.5 g Total 180.0 g
  • Diclofenac sodium, light silicic anhydride, and fumaric acid were kneaded with a solution of methacrylic acid copolymer L in ethanol, dried and pulverized to obtain granules. The granules were suspended in molten Witepsol H15 and poured into containers to obtain sustained-release suppositories, each weighing 1.8 g.
  • Diclofenac sodium 5.0 g Fumaric acid 8.0 g
  • Light silicic anhydride 25.5 g Methacrylic acid copolymer L 5.0 g Witepsol H15 136.5 g Total 180.0 g
  • Diclofenac sodium was suspended in molten Witepsol H5 and poured into containers to obtain suppositories, each weighing 1 g.
  • Diclofenac sodium 2.5 g Witepsol H5 97.5 g Total 100.0 g
  • Indomethacin was suspended in molten Witepsol H5 and poured into containers to obtain suppositories, each weighing 1 g. Indomethacin 2.5 g Witepsol H5 97.5 g Total 100.0 g
  • Ketoprofen was suspended in molten Witepsol H5 and poured into containers to obtain suppositories, each weighing 1 g. Ketoprofen 2.5 g Witepsol H5 97.5 g Total 100.0 g
  • Diclofenac sodium was suspended in molten Witepsol H15 and poured into containers to obtain suppositories, each weighing 1.8 g.
  • Release tests of active components from the sustained-release suppository prepared in Example 1 and the suppository prepared in Comparative Example 1 were carried out by using a suppository dissolution tester (TMS-103) manufactured by Toyama Sangyo Co., Ltd., Osaka, Japan.
  • TMS-103 suppository dissolution tester
  • a phosphate buffer solution prepared by diluting a pH 7.2 phosphate buffer, defined in the chapter of reagents and solutions in the Pharmacopoeia of Japan (11th Edition), to a volume of 10 times (37°C) was used as a receptor solution.
  • the donor charge cell and the receptor phase were partitioned by an artificial membrane (millipore filter) having 0.8 ⁇ m pores. Compartments for the receptor and the receptor phase were stirred at a rate of 25 rpm and 100 rpm, respectively. The results are shown in Figure 1.
  • Example 1 containing fumaric acid in an amount of 0.02 part by weight or more of the active component manifestly exhibited controlled release as compared with the suppository of Comparative Example 1 which contained no fumaric acid.
  • compositions 4-6 The sustained-release suppositories prepared in Example 1 (Compositions 4-6), the sustained-release suppository prepared in Example 2, and the suppository prepared in Comparative Example 1 were administered to male rabbits, weighing 2-2.5 kg. After the administration, blood samples were collected at predetermined time. Plasma diclofenac sodium concentrations were determined by high performance liquid chromatography. The results are shown in Figure 4.
  • the suppositories of the present invention exhibited well-controlled release of the active component, showed neither a rapid increase nor rapid decrease in the blood concentration.
  • the sustained-release suppository preparation of the present invention can control the release of acidic drugs or salts thereof contained therein to the sites where they are absorbed. As a result, their effective blood concentration can be maintained without a rapid increase, thus ensuring remarkable promotion of the therapeutic effects by the drugs.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
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  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Un supositoire à libération entretenue contient un médicament acide ou un sel absorbables par application rectale et un matériau acide ou un tampon de pH. Ce supositoire n'entraîne pas une augmentation abrupte de la concentration du médicament dans le sang immédiatement après son application et a une action prolongée, de sorte qu'il est non seulement plus sûr mais a également d'excellents effets thérapeutiques.
EP90907483A 1988-12-07 1990-05-24 Supositoire a liberation entretenue Expired - Lifetime EP0531524B1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
JP63309596A JPH0816051B2 (ja) 1988-12-07 1988-12-07 徐放性坐剤
PCT/JP1990/000666 WO1991017742A1 (fr) 1988-12-07 1990-05-24 Supositoire a liberation entretenue
CA002083385A CA2083385C (fr) 1988-12-07 1990-05-24 Suppositoire a degagement prolonge
US08/215,970 US5500221A (en) 1988-12-07 1994-03-18 Sustained release suppository

Publications (3)

Publication Number Publication Date
EP0531524A1 true EP0531524A1 (fr) 1993-03-17
EP0531524A4 EP0531524A4 (en) 1993-05-05
EP0531524B1 EP0531524B1 (fr) 1996-03-20

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ID=37188940

Family Applications (1)

Application Number Title Priority Date Filing Date
EP90907483A Expired - Lifetime EP0531524B1 (fr) 1988-12-07 1990-05-24 Supositoire a liberation entretenue

Country Status (6)

Country Link
US (1) US5500221A (fr)
EP (1) EP0531524B1 (fr)
JP (1) JPH0816051B2 (fr)
CA (1) CA2083385C (fr)
DE (1) DE69026115T2 (fr)
WO (1) WO1991017742A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1116489A1 (fr) * 1998-09-21 2001-07-18 Amato Pharmaceutical Products, Ltd. Systeme d'administration orale de medicament permettant d'ameliorer la biodisponibilite de la glycyrrhetine activee
WO2003026624A1 (fr) * 2001-09-28 2003-04-03 Mcneil-Ppc, Inc. Formes pharmaceutiques a liberation modifiee

Families Citing this family (12)

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Publication number Priority date Publication date Assignee Title
US6200590B1 (en) 1998-08-10 2001-03-13 Naphcare, Inc. Controlled, phased-release suppository and its method of production
DE19920415A1 (de) * 1999-05-04 2000-11-09 Hexal Ag Metamizol enthaltende, kontrolliert freisetzende pharmazeutische Zusammensetzung
US20020103110A1 (en) * 2001-01-26 2002-08-01 Spitzer A. Robert System and method for rectal administration of medication for treatment of migraines
TNSN02063A1 (en) * 2001-07-07 2005-12-23 Egyptian Natural Oil Co Natoil The medical effect of jojoba oil
US7838026B2 (en) 2001-09-28 2010-11-23 Mcneil-Ppc, Inc. Burst-release polymer composition and dosage forms comprising the same
US7122143B2 (en) 2001-09-28 2006-10-17 Mcneil-Ppc, Inc. Methods for manufacturing dosage forms
EP1348436A1 (fr) * 2002-03-30 2003-10-01 Boehringer Ingelheim International GmbH Suppositoires de meloxicam
US7807197B2 (en) 2002-09-28 2010-10-05 Mcneil-Ppc, Inc. Composite dosage forms having an inlaid portion
US20050282011A1 (en) * 2004-06-21 2005-12-22 Nissin Chemical Industry Co., Ltd. Microcapsule emulsion and method for producing the same
US8436051B2 (en) * 2007-06-08 2013-05-07 Aptalis Pharma Canada Inc. Mesalamine suppository
US7541384B2 (en) 2007-06-08 2009-06-02 Axcan Pharma Inc. Mesalamine suppository
US8217083B2 (en) * 2007-06-08 2012-07-10 Aptalis Pharma Canada Inc. Mesalamine suppository

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JPS57158719A (en) * 1981-03-24 1982-09-30 Fujisawa Pharmaceut Co Ltd Rectal administration pharmaceutical
US4542020A (en) * 1984-08-17 1985-09-17 E. R. Squibb & Sons, Inc. Long-lasting adhesive antifungal suppositories
JPS60224621A (ja) * 1984-04-20 1985-11-09 Fujisawa Pharmaceut Co Ltd 抗リウマチ剤

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JPS55149209A (en) * 1979-05-10 1980-11-20 Kyoto Yakuhin Kogyo Kk Composition for rectal administration
JPS56138111A (en) * 1980-03-28 1981-10-28 Teijin Ltd Suppository containing unsaturated fatty acid or salt thereof
JPS56138110A (en) * 1980-03-28 1981-10-28 Teijin Ltd Suppository containing citric acid or salt thereof
JPS56138112A (en) * 1980-03-31 1981-10-28 Teijin Ltd Suppository containing ascorbic acid or sodium ascorbate
JPS5838210A (ja) * 1981-08-31 1983-03-05 Taiho Yakuhin Kogyo Kk 直腸投与用製剤
JPS58103326A (ja) * 1981-12-11 1983-06-20 Kao Corp 坐薬用基剤組成物
JPS6284018A (ja) * 1985-10-09 1987-04-17 Kao Corp 坐剤

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Publication number Priority date Publication date Assignee Title
JPS57158719A (en) * 1981-03-24 1982-09-30 Fujisawa Pharmaceut Co Ltd Rectal administration pharmaceutical
JPS60224621A (ja) * 1984-04-20 1985-11-09 Fujisawa Pharmaceut Co Ltd 抗リウマチ剤
US4542020A (en) * 1984-08-17 1985-09-17 E. R. Squibb & Sons, Inc. Long-lasting adhesive antifungal suppositories

Non-Patent Citations (3)

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Title
DATABASE WPIL Section Ch, Week 8245, Derwent Publications Ltd., London, GB; Class B01, AN 82-96018E & JP-A-57 158 719 (FUJISAWA PHARM KK) 30 September 1982 *
DATABASE WPIL Section Ch, Week 8551, Derwent Publications Ltd., London, GB; Class A12, AN 85-320783 & JP-A-60 224 621 (FUJISAWA PHARM KK) 9 November 1985 *
See also references of WO9117742A1 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1116489A1 (fr) * 1998-09-21 2001-07-18 Amato Pharmaceutical Products, Ltd. Systeme d'administration orale de medicament permettant d'ameliorer la biodisponibilite de la glycyrrhetine activee
EP1116489A4 (fr) * 1998-09-21 2002-06-05 Amato Pharm Prod Ltd Systeme d'administration orale de medicament permettant d'ameliorer la biodisponibilite de la glycyrrhetine activee
WO2003026624A1 (fr) * 2001-09-28 2003-04-03 Mcneil-Ppc, Inc. Formes pharmaceutiques a liberation modifiee

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Publication number Publication date
CA2083385A1 (fr) 1991-11-25
JPH0816051B2 (ja) 1996-02-21
DE69026115D1 (de) 1996-04-25
WO1991017742A1 (fr) 1991-11-28
EP0531524B1 (fr) 1996-03-20
CA2083385C (fr) 2000-02-22
US5500221A (en) 1996-03-19
EP0531524A4 (en) 1993-05-05
JPH02157220A (ja) 1990-06-18
DE69026115T2 (de) 1996-10-31

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